Generation and regulation of autocytotoxicity in mixed lymphocyte cultures: evidence for active suppression of autocytotoxic cells.

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Abstract
Using limiting dilution analysis, both the generation and suppression of autocytotoxic cells were detected following autologous or allogeneic stimulation in vitro. Assay conditions were established in which the cytotoxic response towards an allogeneic sensitizing cell was consistent with a traditional single-hit kinetic model. Under identical conditions, cytolytic activity toward autologous phytohemagglutinin-activated lymphocytes exhibited a distinct biphasic response. At low responder cell doses, a clear autocytotoxic response was observed. At higher responder cell numbers, this autocytotoxic reaction disappeared. This biphasic pattern of autocytotoxicity developed after stimulation with allogeneic or autologous peripheral blood mononuclear leukocytes (PBL) or Epstein-Barr virus-transformed B cells. This pattern of response is consistent with the counterpoised actions of 2 distinct cell populations, an autoaggressive population and a lower frequency autosuppressor population. Autocytotoxicity was not the result of mitogenic or xenogeneic antigenic stimulation, as it was observed after stimulation with autologous PBL in autologous serum and an autologous interleukin 2 preparation. Cells capable of autocytotoxicity are present in peripheral blood but at a lower frequency than allocytotoxic T lymphocytes. Autoaggressive cells are down-regulated by an autologous suppressor population. Immunologic self-tolerance may at least in part, be an actively maintained condition. Disturbances in this autoregulatory network may have relevance to the pathogenesis of some autoimmune diseases and graft-vs.-host disease.

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